The application of chemically synthesized oligonucleotides to biochemical and biological questions is to be investigated. Making use of the Watson-Crick complementarity principle, the validity of a nucleic acid ribosomal (Shine-Dalgarno) binding site is to be studied. A series of nucleic acid fragments complementary to ribosomal RNA (16S) are to be constructed, and interference with the binding of messenger RNA in a prokaryotic system is to be examined. A series of variants for this site, including analogs with nuclease-resistant internucleotide linkages, and sequences bearing allowable mutations are to be provided with a view to finding useful inhibitors for protein synthesis. Extension to irreversible inhibitors by the attachment of alkylating moieties is to be studied.